Although glycochemistry has developed in leaps and bounds in the last decade or so, the synthesis of a complex oligosaccharide or of a glycoconjugate remains a very challenging albeit critically important task. The difficulties inherent in such syntheses arise because of numerous reasons that center on the complexity of the chemistry when compared to that of oligonucleotide and peptide synthesis. The most important reactions in any oligosaccharide synthesis are the formation of the glycosidic bonds and there exists an absolutely overwhelming number of methods toward this end. Unfortunately the vast majority of these methods have been developed empirically, are therefore underpinned by very little detailed understanding of mechanism, and have very little generality. The underlying theme of this proposal is that the challenge of the simplification of complex oligosaccharide synthesis is best met by an improved understanding of the mechanisms of glycosidic bond formation, coupled with the development of more efficient, straightforward and general mechanism-based methods. A necessary step toward this goal is the detailed investigation of the mechanisms of glycosylation mechanisms, and accordingly this proposal addresses several issues considered critical to the resolution of this problem. The issues to be addressed include the development of methods for the spectroscopic identification and study of glycosyl oxocarbenium ions, the development of NMR-based kinetic isotope effect methods for the study of glycosylation kinetics, the development of mass spectrometry-based methods for the study of the influence of protecting groups on oxocarbenium ion stability, and the development of improved glycosylation systems based these studies of mechanism.